Inhibition of tissue transglutaminase sensitizes TRAIL-resistant lung cancer cells through upregulation of death receptor 5

Frese-Schaper, Manuela; Schardt, Julian A; Sakai, Toshiyuki; Carboni, Giovanni L; Schmid, Ralph A; Frese, Steffen (2010). Inhibition of tissue transglutaminase sensitizes TRAIL-resistant lung cancer cells through upregulation of death receptor 5. FEBS letters, 584(13), pp. 2867-71. Amsterdam: Elsevier 10.1016/j.febslet.2010.04.072

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Tissue transglutaminase (TG2) is implicated in cellular processes such as apoptosis and cell migration. Its acyl transferase activity cross-links certain proteins, among them transcription factors were described. We show here that the TG2 inhibitor KCC009 reversed resistance to tumor necrosis factor-related apoptosis-inducing factor (TRAIL) in lung cancer cells. Sensitization required upregulation of death receptor 5 (DR5) but not of death receptor 4. Upregulation of DR5 involved the first intron of the DR5 gene albeit it was independent from p53 and nuclear factor kappa B. In conclusion, inhibition of tissue transglutaminase provides an interesting strategy for sensitization to TRAIL-induced apoptosis in p53-deficient lung cancer cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery

UniBE Contributor:

Frese, Manuela; Carboni, Giovanni Luca; Schmid, Ralph and Frese, Steffen R.

ISSN:

0014-5793

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:07

Last Modified:

04 May 2014 23:04

Publisher DOI:

10.1016/j.febslet.2010.04.072

PubMed ID:

20450916

Web of Science ID:

000278657200025

URI:

https://boris.unibe.ch/id/eprint/279 (FactScience: 197297)

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